Mostrar el registro sencillo del ítem
dc.contributor.author
Ruggiero, Melina
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Kerff, Frédéric
dc.contributor.author
Herman, Raphaël
dc.contributor.author
Sapunaric, Frédéric
dc.contributor.author
Galleni, Moreno
dc.contributor.author
Gutkind, Gabriel Osvaldo
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Charlier, Paulette
dc.contributor.author
Sauvage, Eric
dc.contributor.author
Power, Pablo
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.date.available
2017-12-13T18:49:25Z
dc.date.issued
2014-07
dc.identifier.citation
Ruggiero, Melina; Kerff, Frédéric; Herman, Raphaël; Sapunaric, Frédéric; Galleni, Moreno; et al.; Crystal Structure of the Extended-Spectrum β-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with β-Lactams and β-Lactamase Inhibitors; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 58; 2; 7-2014; 5994-6002
dc.identifier.issn
0066-4804
dc.identifier.uri
http://hdl.handle.net/11336/30513
dc.description.abstract
PER-2 belongs to a small (7 members to date) group of extended-spectrum β-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies towards most β-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 Å, and evaluated the possible role of several residues in the structure and activity towards β-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular trans bond between residues 166-167 that generates an inverted Ω loop, and an expanded fold of this domain that results in a wide active site cavity that allows for an efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A β-lactamases. PER β-lactamases could be included within a cluster of evolutionary related enzymes harboring conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A, with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different β-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-Water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we could expect that mutations occurring in these positions will have impact in the overall hydrolytic behavior.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
X-Ray Crystallography
dc.subject
Esbl
dc.subject
Oxyimino-Cephalosporins
dc.subject
Per-1
dc.subject
Arg220
dc.subject
Clavulanic Acid
dc.subject
Thr237
dc.subject.classification
Otras Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Crystal Structure of the Extended-Spectrum β-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with β-Lactams and β-Lactamase Inhibitors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-12-12T18:28:52Z
dc.identifier.eissn
1098-6596
dc.journal.volume
58
dc.journal.number
2
dc.journal.pagination
5994-6002
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Washington DC
dc.description.fil
Fil: Ruggiero, Melina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
dc.description.fil
Fil: Kerff, Frédéric. Université de Liège; Bélgica
dc.description.fil
Fil: Herman, Raphaël. Université de Liège; Bélgica
dc.description.fil
Fil: Sapunaric, Frédéric. Université de Liège; Bélgica
dc.description.fil
Fil: Galleni, Moreno. Université de Liège; Bélgica
dc.description.fil
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
dc.description.fil
Fil: Charlier, Paulette. Université de Liège; Bélgica
dc.description.fil
Fil: Sauvage, Eric. Université de Liège; Bélgica
dc.description.fil
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
dc.journal.title
Antimicrobial Agents and Chemotherapy
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/58/10/5994.abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.00089-14
Archivos asociados